Isolation of Intermediates in the Synthesis of Thieno[2,3-d]pyrimidine-2,4(1H,3H)-diones Using Microwave Irradiation

A simple and fast method for the isolation of intermediates in the synthesis of 3-arylthieno[2,3-d]pyrimidine-2,4(1H,3H)-diones has been developed by microwave-assisted condensation of ethyl 2-amino-4,5-dimethylthiophene-3-carboxylate with aryl isocyanates. The intermediates, subsequently, underwent cyclization in t-butanol in the presence of potassium t-butoxide on heating to reflux to give the desired bicyclic products, 3-arylthieno[2,3-d]pyrimidine-2,4(1H,3H)-diones.     

Efficient,One-Pot Synthesis of Triazolothiadiazinyl-pyrazolone and Pyrazolyl-triazolothiadiazine Derivatives via Multicomponent Reaction

A one-pot, multicomponent reaction of 3-(2-bromo acetyl)coumarins, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and different derivatives of ethyl 2-(2-(aryl)hydrazono)-3-oxobutanoates provide an efficient and direct method for the synthesis of 4-(arylydrazono)-3-methyl-1-(6-(coumarin-3-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)-1H-pyrazol-5(4H)-ones (4a–h). A similar methodology was also developed for the synthesis of pyrazolyl-triazolothiadiazines (9a–f) using acetyl acetone, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and different derivatives of phenacylbromide. The resulting products were characterized by analytical and spectral data.     

A facile one-pot synthesis of new thieno- [2,3-d]pyrimidine-2,4（1H,3H）-dione derivatives

A facile one-pot synthesis of new 3-arylthieno[2,3-d]pyrimidine-2,4(1H,3H)-diones via base-catalyzed cyclocondensation of ethyl 2-amino-4,5-dimethylthiophene-3-carboxylate with aryi isocyanates is described.     

Domino reaction of 3-(2-formylphenoxy)propenoates and amines: a novel synthesis of 1,4-dihydropyridines from salicaldehydes, ethyl propiolate, and amines

A novel synthesis of Hantzsch-type N-substituted 1,4-dihydropyridines from salicaldehydes, ethyl propiolate, and amines has been developed. Salicaldehydes were treated with ethyl propiolate in the presence of N-methylmorpholine to give ethyl 3-(2-formylphenoxy)propenoates. Three equivalents of ethyl 3-(2-formylphenoxy)propenoates reacted with 1 equiv of amines under trifluoroacetic acid (TFA) catalyst to furnish the corresponding N-substituted 1,4-dihydropyridines in good to excellent yields, recovering the starting material salicaldehydes. A possible mechanism for the domino process was proposed. Furthermore, the products can be easily derived via further transformations and three of them exhibited strong fluorescence (Phif = 0.36-0.63).     

Condensation of Ethyl 2-Oxoindoline-3-glyoxylate with o-Aminophenol and o-Phenylenediamine

A method is presented for the synthesis of 3-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)-1,4-dihydroquinoxalin-2-one and 2-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2H-1,4-benzoxazin-3(4H)-one by the reaction of ethyl 2-oxoindoline-2-glyoxylate with o-aminophenol and o-phenylenediamine. Proposed reaction mechanisms are presented.     

Total synthesis of two novel 5,6,7,8-tetrahydroindolizine alkaloids, polygonatines A and B

The structures of polygonatines A and B, two simple but structurally novel alkaloids, have been substantiated by synthesis. Cyclisation of 4-(1H-pyrrol-1-yl)butanoic acid or its ethyl ester produced 6,7-dihydroindolizin-8(5H)-one , formylation of which at C-3 followed by reduction afforded polygonatine A . Acetylation of this alkaloid followed by displacement of the acetate with ethanol yielded polygonatine B , possibly via an azafulvenium cation.     

An efficient one-pot synthesis of thiophene-fused pyrido[3,2-a]azulenes via Gewald reaction

A simple and efficient procedure was developed for the synthesis of 11H(2H)-4-oxothiophene[3',4':6,5]pyrido[3,2-a]azulene-10-carboxylates(3) in moderate to good yields via the Gewald reaction of ethyl 1-cyanoacetyl-2-methoxyazulene-3-carboxylate(1) with carbonyl compounds(2) and elemental sulfur utilizing imidazole as catalyst.This reaction provides a new procedure for synthesis of pyridinone-fused azulenes.     

Nucleotides. Part XXVII Bis[2-(p-nitrophenyl)ethyl] Phosphorochloridate,a New Versatile Phosphorylating Agent in Nucleotide Chemistry

A new, versatile phosphorylating agent, bis[2-(p-nitrophenyl)ethyl] phosphorochloridate ( 3 ), has been prepared and is used for 3′- and/or 5′-phosphorylations of nucleosides. The resulting bis[2-(p-nitrophenyl)ethyl] phosphotriesters are versatile synthons in oligonucleotide synthesis leading finally to 3′- and/or 5′-terminated monophosphates in excellent yields.     

Facile One-Pot Synthesis of Aryl,Heteryl Substituted Hydrazono Thiazolyl-Pyrazolone Derivatives via Three-Component Reaction

A facile, one-pot, three-component bis heterocyclized reaction for the synthesis of hydrazonothiazolyl-pyrazolones has been described. Reaction of phenacyl bromides or 3-(2-bromoacetyl)coumarins, with thiosemicarbazide and ethyl 2-(2-arylhydrazono)-3-oxobutanoates in AcOH/NaOAc, gave the corresponding products in good yields. All the synthesized compounds were characterized by their analytical and spectral data.     

Synthesis of a tritium-labeled, fipronil-based, highly potent, photoaffinity probe for the GABA receptor

3-[4-[1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazolo]]-3-(trifluoromethyl)diazirine is a fipronil-based (i.e. fiprole), high-affinity probe for the GABA receptor. For synthesis of the tritium-labeled version of this trifluoromethyldiazirinylfiprole ([(3)H]TDF) the required intermediate, 3-[4-[1-(2,6-dichloro-3-iodo-4-trifluoromethylphenyl)-5-iodopyrazolo]]-3-(trifluoromethyl)diazirine, was prepared in 10 steps from pyrazole and 3,5-dichloro-4-fluorobenzotrifluoride. One of the key transformations was lithiation and subsequent iodination of the 4-(2,2,2-trifluoro-1-hydroxyethyl)pyrazole intermediate. The last step involved reduction of the diiodofiprole with tritium, Pd/C, and triethylamine in ethyl acetate and afforded [(3)H]TDF with a specific activity of 15 Ci/mmol and 99% radiopurity.     

Family of mixed-valence oxovanadium(IV/V) dinuclear entities incorporating N4O3-coordinating heptadentate ligands: synthesis, structure, and EPR spectra

Dinuclear (V(IV)V(V)) oxophenoxovanadates of general formula [V2O3L] have been synthesized in excellent yields by reacting bis(acetylacetonato)oxovanadium(IV) with H3L in a 2:1 ratio in acetone under an N2 atmosphere. Here L3- is the deprotonated form of 2,6-bis[{{(2-hydroxybenzyl)(N',N'-(dimethylamino)ethyl)}amino}methyl]-4-methylphenol (H3L1), 2,6-bis[{{(5-methyl-2-hydroxybenzyl)(N',N'-(dimethylamino)ethyl)}amino}methyl]-4-methylphenol (H3L2), 2,6-bis[{{(5-tert-butyl-2-hydroxybenzyl)(N',N'-(dimethylamino)ethyl)}amino}methyl]-4-methylphenol (H3L3), 2,6-bis[{{(5-chloro-2-hydroxybenzyl)(N',N'-(dimethylamino)ethyl)}amino}methyl]-4-methylphenol(H3L4), 2,6-bis[{{(5-bromo-2-hydroxybenzyl)(N'N'-(dimethylamino)ethyl)}amino}methyl]-4-methylphenol (H3L5), or 2,6-bis[{{(5-methoxy-2-hydroxybenzyl)(N'N'-(dimethylamino)ethyl)}methyl]-4-methylphenol (H3L6). In [V2O3L1], both the metal atoms have distorted octahedral geometry. The relative disposition of two terminal V=O groups in the complex is essentially cis. The O=V...V=O torsion angle is 24.6(2) degrees . The V-O(oxo)-V and V-O(phenoxo)-V angles are 117.5(4) and 93.4(3) degrees , respectively. The V...V bond distance is 3.173(5) A. X-ray crystallography, IR, UV-vis, and 1H and 51V NMR measurements show that the mixed-valence complexes contain two indistinguishable vanadium atoms (type III). The thermal ellipsoids of O2, O4, C10, C14, and C15 also suggests a type III complex in the solid state. EPR spectra of solid complexes at 77 K display a single line indicating the localization of the odd electron (3d(xy)1). Valence localization at 77 K is also consistent with the 51V hyperfine structure of the axial EPR spectra (3d(xy)1 ground state) of the complexes in frozen (77 K) dichloromethane solution: S = 1/2, g(parallel) approximately 1.94, g(perpendicular) approximately 1.98, A(parallel) approximately 166 x 10(-4) cm(-1), and A(perpendicular) approximately 68 x 10(-4) cm(-1). In contrast isotropic room-temperature solution spectra of the family have 15 hyperfine lines (g(iso) approximately 1.974 and A(iso) approximately 50 x 10(-4) cm(-1)) revealing that the unpaired electron is delocalized between the metal centers. Crystal data for the [V2O3L1].CH2Cl2 complex are as follows: chemical formula, C32H43O6N4Cl2V2; crystal system, monoclinic; space group, C2/c; a = 18.461(4), b = 17.230(3), c = 13.700(3) A; beta = 117.88(3) degrees ; Z = 8.     

Excited-state decay of hydrocarbon radicals, investigated by femtosecond time-resolved photoionization: ethyl, propargyl, and benzyl

The excited state decay of the hydrocarbon radicals ethyl, C(2)H(5); propargyl, C(3)H(3); and benzyl, C(7)H(7) was investigated by femtosecond time-resolved photoionization. Radicals were generated by flash pyrolysis of n-propyl nitrite, propargyl bromide, and toluene, respectively. It is shown that the 2 (2)A(') (3s) Rydberg state of ethyl excited at 250 nm decays with a time constant of 20 fs. No residual signal was observed at longer delay times. For the 3 (2)B(1) state of propargyl excited at 255 nm a slower decay with a time constant 50+/-10 fs was determined. The 4 (2)B(2) state of benzyl excited at 255 nm decays within 150+/-30 fs.     

Synthesis, Cardiovascular Activity, and Electrochemical Oxidation of Nitriles of 5-Ethoxycarbonyl-2-methylthio-1,4-dihydropyridine-3-carboxylic Acid

Nitriles of 4-aryl-5-ethoxycarbonyl-2-methylthio-1,4-dihydropyridine-3-carboxylic acid have been obtained by the methylation of 1,4-dihydropyridine-2-thiolates; of 1,4-dihydropyridine-2(3H)-thiones in the presence of a stoichiometric amount of piperidine, and of a mixture of 1,4,5,6-tetrahydro- and 1,4-dihydropyridine-2-thiolates with methyl iodide. One-pot multicomponent synthesis has also been used in the condensation of ethyl 2-arylmethyleneacetoacetate, 2-cyanothioacetamide, piperidine, and methyl iodide; of ethyl acetoacetate, 3-aryl-2-cyanothioacrylamide, piperidine, and methyl iodide; and of ethyl acetoacetate, an aromatic aldehyde, 2-cyanothioacetamide, piperidine, and methyl iodide. The latter, a five-component method, takes place rapidly and under mild conditions, it is efficient (yields of 75-96%, economy of time, labour, and resources) and green (there is no need to synthesize lachrymators, such as 3-aryl-2-cyanothioacrylamides).The cardiovascular activity and the electrochemical oxidation of the synthesized 2-methylthio-1,4-dihydropyridines have been investigated. A comparative analysis has been carried out of the ability towards electrochemical oxidation as a function of the electronic properties of the substituent at position 4 of the heterocycle.     

Synthesis of Ethyl 5-(Arylcarbamoyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylates

Russian Journal of Organic Chemistry - A one-step procedure has been developed for the synthesis of previously unknown ethyl 5-(arylcarbamoyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylates by...     

New,Convenient, One-Pot Method for the Synthesis of Thiazolyl-pyrazolones from Dehydroacetic Acid Derivative via a Multicomponent Approach

A convenient one-pot method for the synthesis of thiazolyl-pyrazolones was described in excellent yields. Reaction of 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one with thiosemicarbazide and ethyl 2-(2-arylhydrazono)-3-oxobutanoates in anhydrous ethanol under reflux conditions afforded the corresponding 4-(2-arylhydrazono)-1-(4-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)thiazol-2-yl)-3-methyl-1H-pyrazol-5(4H)-one in good yields. The structures of newly synthesized compounds were established on the basis of elemental analysis, infrared, ¹H NMR, and mass spectroscopic studies.     

Synthesis of a ligand based upon a new entry into the 3-hydroxy-N-alkyl-2(1H)-pyridinone ring system and thermodynamic evaluation of its gadolinium complex

The synthesis of a new, more water soluble derivative of TREN-Me-3,2-HOPO (tris[(3-hydroxy-1-methyl-2-oxo-1,2- didehydropyridine-4-carboxamido)ethyl]amine) is presented. The synthesis starts with the condensation reaction of (N-methoxyethylamino)acetonitrile hydrochloride and oxalyl chloride to give 3,5-dichloro-N-(methoxyethyl)-2(1H)-pyrazinone. The 3-position is readily substituted with a benzyloxy group, and the pyrazinone is converted to ethyl 3-(benzyloxy)-N-(methoxyethyl)-2(1H)-pyridinone-4-carboxylate by a Diels-Alder cycloaddition with ethyl propiolate. Basic deprotection of the ester followed by activation, coupling to tren, and acidic deprotection of the benzyl groups gives the ligand TREN-MOE-3,2-HOPO (tris[(3-hydroxy-1-(methoxyethyl)- 2-oxo-1,2-didehydropyridine-4-carboxamido)ethyl]amine). The gadolinium complex of TREN-MOE-3,2-HOPO was prepared by metathesis, starting from gadolinium chloride. The solubility of the new metal complex is significantly enhanced. The four protonation constants (determined by potentiometry) for TREN-MOE-3,2-HOPO (log Ka1 = 8.08, log Ka2 = 6.85, log Ka3 = 5.81, log Ka4 = 4.98) are virtually identical to those reported for the parent ligand. The stability constants for the gadolinium complex of TREN-MOE-3,2-HOPO determined by potentiometry (log beta 110 = 19.69(2), log beta 111 = 22.80(2)) and by spectrophotometry (log beta 110 = 19.80(1), log beta 111 = 22.88(1), log beta 112 = 25.88(1)) differ slightly from those for the parent ligand; this follows from a change in the complexation model in which a new diprotonated species, [Gd(TREN-MOE-3,2-HOPO)(H)2]2+, was included. The presence of this extra species was demonstrated by factor analysis, comparison of spectral data, and nonlinear least-squares refinement. Significant formation of this species is observed between pH 3 and pH 1.5.     

Synthesis of 5-[2-(Phenoxy)ethyl] Derivatives of 6-Methyluracil, 6-Methyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one,and 2-Imino-6-methyl-2,3-dihydro-1H-pyrimidin-4-one

A synthesis of novel derivatives of 6-methyluracil, 6-methyl-2-thioxo-, and 2-imino-6-methyl-2,3-dihydro-1H-pyrimidin-4-one containing a 2-(phenoxy)ethyl substituent at position 5 of the pyrimidine ring has been carried out. It was found that 5-[2-(phenoxy)ethyl] derivatives of 6-methyl-2-thioxo- and 2-imino-6-methyl-2,3-dihydro-1H-pyrimidin-4-one are obtained by the condensation of the corresponding ethyl 3-oxo-2-(2-phenoxyethyl)butanoates with thiourea or guanidine. 6-Methyl-5-[2-(phenoxy)ethyl]uracils can be prepared by treating 6-methyl-5-[2-(phenoxy)ethyl]-2-thioxo-2,3-dihydro-1H-pyrimidin-4-ones with an excess of aqueous monochloroacetic acid solution. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1213–1217, August, 2005.     

离子液体[2-aemim]im催化Knoevenagel反应和异噁唑酮合成

以碱性离子液体1-(2-氨基乙基)-3-甲基咪唑咪唑盐([2-aemim]im)作为催化剂,催化Knoevenagel反应和4-芳亚甲基异噁唑-5(4H)-酮衍生物的合成。实验结果表明:在无溶剂条件下,该离子液体对Knoevenagel反应具有很高的催化活性,一系列芳香醛和活泼亚甲基化合物的反应在室温条件下2 min内顺利完成,均以90%以上的高产率生成取代烯烃产物.将该碱性离子液体用于催化乙酰乙酸乙酯或苯甲酰乙酸乙酯、盐酸羟胺和芳香醛三组分一锅法缩合制备4-芳亚甲基异噁唑-5(4H)-酮衍生物,具有反应时间较短、产率较高和后处理简单的特点。离子液体经简单处理后能多次循环使用。     

Fluorous tag method for the simultaneous synthesis of different kinds of glycolipids

A mixture of saccharide primers with partially fluorinated tails, 2-(perfluorooctyl)ethyl 4′-O-(β-d-galactopyranosyl)-β-d-glucopyranoside (Lac H2F8) and 6-(perfluorohexyl)hexyl 2′-acetamido-2′-deoxy-β-d-glucopyranoside (GN H6H6), were introduced to animal cells. The oligosaccharide of Lac H2F8 was elongated by cellular enzymes and gave a GM3-type oligosaccharide. On the other hand, GN H6F6 was galactosylated to afford a lactosamine derivative that was further sialylated. This research confirmed that simultaneous glycosylation processes took place for Lac H2F8 and GN H6F6 primers and that the presence of one did not prevent the glycosylation of the other from proceeding. Each primer was recognized independently and elongated sequentially by cellular enzymes. Significantly, the synthesis of glycolipids from a mixture of these artificial scaffolds did not prevent the synthesis of glycolipids from the natural precursor. The glycosyl transferases recognized both precursors resulting to simultaneous synthesis of glycolipids.     

A facile synthesis of 6-amino-2H, 4H-pyrano[2,3-F]pyrazole-5-carbonitriles in deep eutectic solvent

A convenient synthesis of 6-amino-2H,4H-pyrano[2,3-F]pyrazole-5-carbonitriles has been accomplished by one pot four-component cyclocondensation of aromatic aldehydes(1a-o) malanonitrile(2), ethyl acetoacetate(3), and hydrazine hydrate(4) in freshly prepared deep eutectic solvent, DES(choline chloride:urea). This protocol has afforded corresponding pyrano[2,3-F]pyrazoles in shorter reaction time with high yields, and it avoids the use of typical toxic catalysts and solvents.